The DOI matches its Crossref record; 156 of the 157 references it cites were found in a registry or an index.
Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy
Open accessAbstract
Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“our findings indicate that by preserving the tissue repopulating capacity of the epithelial stem cells, mTOR inhibition with rapamycin and newly developed agents (Wander et al., 2011) may prevent the appearance of radiation-induced mucositis and its consequent negative impact on anticancer treatment outcome and cost”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Wander et al., 2011
In the citing paper
“Treatments targeting key components of tumor hypoxia signaling pathways, including mTOR, are one of the current approaches to cancer therapy.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [182]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
AKT/PKB signaling: navigating downstream
Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15593 · Cited by 4,794
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma
Hudes, G. R., Carducci, M. A., Tomczak, P., Dutcher, J. P., Figlin, R. A., Kapoor, A., Starosławska, E., Sosman, J. A., McDermott, D. F., Bodrogi, I., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa066838 · Cited by 3,645
Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., Haqq, A. M., Shah, S. H., Arlotto, M., Slentz, C. A., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.02.002 · Cited by 3,165
Flagged first, then by citations
1 of the 157 references couldn’t be matched to a known paper.
Research works printed but not linked: 7
- Knowles, 2003, Cancer Res., 63, 7652
- Chawla, 2006, J Clin Oncol., 24(suppl), 521s
- Colombo, 2007, J Clin Oncol., 25(suppl), 278s
- Slomovitz, 2008, J Clin Oncol., 26(suppl), 293s
- Carracedo, 2008, J Clin Invest., 118, 3065
- Chow LWC, et al. Presented at the 29th Annual San Antonio Breast Cancer Symposium (December 14–17, 2006, San Antonio, Texas, USA), Phase III study of temsirolimus with letrozole or letrozole alone in postmenopausal women with locally advanced or metastatic breast cancer.
- Shi, 2002, Cancer Res., 62, 5027
Cited by
Sorted by citations
Items 401–429 of 429
The role of mTORC2 in mammary morphogenesis and HER2-mediated tumorigenesis
Morrison, M. M. (2015)
New Approaches for the Treatment of Triple Negative Breast Cancer
Sulaiman, A. (2019) · uO Research (University of Ottawa) · doi:10.20381/ruor-23348
Efficacy of Everolimus in Treating Breast Cancer
Punukula, H. C. (2020) · International Journal of Pharmaceutical Sciences Review and Research · doi:10.47583/ijpsrr.2020.v65i01.007
Activated mTORC1-SIRT6 Mediates Myofibroblast Differentiation and Idiopathic Pulmonary FibrosisPreprint
Zhang, J., Hu, Y., Huang, H., Liu, Q., Du, Y., Wang, G., Gao, D., Guo, W., Wang, Z., & Ma, A. (2021) · Research Square · doi:10.21203/rs.3.rs-587874/v1
Fiddle Songs and Banjo Songs: A Description Index
Howard, G. W. (1981) · TopSCHOLAR (Western Kentucky University)
Regulation of the Mechanistic Target of Rapamycin by Cellular Stress.
Magnuson, B. (2013) · Deep Blue (University of Michigan)
Tolerancia Inmunologica en trasplante renal
Gómez, F. M. H. (2014) · doi:10.35376/10324/8548
CDK Inhibitors in Normal and Malignant Cells
Besser, A. H., & Slingerland, J. M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.00221-2
Self-citationMizera, S. M. (2022) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-9485
Wang, Z., Feng, X., Molinolo, A., Martı́n, D., Vitale-Cross, L. A., Nohata, N., Ando, M., Wahba, A., Amornphimoltham, P., Wu, X., et al. (2023) · doi:10.1158/0008-5472.c.6511397.v1
Li, J., Li, Q., Chen, X., & Yu, Y. (2025) · International Journal of Ophthalmology · doi:10.18240/ijo.2025.04.02
Autophagy and Neurodegenerative Diseases
Barbosa, A. D., Palmer, J. E., Li, X., & Rubinsztein, D. C. (2025) · Learning materials in biosciences · doi:10.1007/978-3-031-88121-3_6
Qiu, C., Gao, S., Li, Z., Liu, H., Chi, S., Wu, S., Zhang, W., & Liu, X. (2025) · Scientific Reports · doi:10.1038/s41598-025-28798-6
Devapatla, P., Teng, Y. G., Settipalli, P. C., Yeruva, P. K. R., Hsieh‐Li, H. M., & Shaik, A. (2025) · The FASEB Journal · doi:10.1096/fj.202503323r
Cormerais, Y. (2016) · theses.fr (ABES) · doi:10.70675/94cc6971z3a1dz454fzb65dzf153dc0a3a05
Conséquences traductionnelles de la perte de 4E-BP1 dans l'adénocarcinome pancréatique
Müller, D. (2016) · theses.fr (ABES) · doi:10.70675/1f894fb2zc2daz446fza7f2z2b28408eb6e2
Ciblage thérapeutique de la réponse au stress cellulaire dans l'ostéosarcome
Moukengué, B. (2019) · theses.fr (ABES) · doi:10.70675/26cb2736z4fbdz42d2zabcbzca5db0a782e1
de Calbiac, H. (2019) · theses.fr (ABES) · doi:10.70675/bafe951fz8332z4b0azb55bzac8a4af1955b
Combination Therapies: Synergizing Treatments for Enhanced Efficacy
Tiwari, P., Dubey, S., & Kadiri, S. K. (2026) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9798898814144126010004
Metabolic Reprogramming of B Cells in Cancer: Effects of Altered Energetics
Sarkar, U. A., Ambareen, N., Prasad, P., Kamran, M., & Ghosh, S. (2026) · Biology · doi:10.3390/biology15100744
Role of molecular target therapies in effective breast cancer treatments
Ghosh, B., Shil, S., & Kumavath, R. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-43846-2.00017-9
Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability
Sainero‐Alcolado, L., Lama, D., Alzrigat, M., & Arsenian‐Henriksson, M. (2026) · BioDrugs · doi:10.1007/s40259-026-00798-6
Small molecule kinase inhibitors: current status and future directions
Chandra, P., Varshney, P. K., Raghav, A., & Sachan, N. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-49074-3.00013-3
Wu, Z., Zhou, K., Wang, N., Yan, J., Lu, Z., Fu, Y., Tong, X., Xiang, Y., Shi, Y., Yang, S., et al. (2026) · Biomaterials · doi:10.1016/j.biomaterials.2026.124719
BindingDB (2021) · UC San Diego · doi:10.7270/q2rr22gw
Metadata
- Authors
- Wander, S. A., Hennessy, B. T., & Slingerland, J. M.
- Affiliations
- University of Miami (US)
- Royal College of Surgeons in Ireland (IE)
- Corresponding author
- Slingerland, Joyce M.
- Venue
- Journal of Clinical Investigation
- Published
- 2011-04-01
- Volume
- 121
- Issue
- 4
- Pages
- 1231-1241
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3069769
- OpenAlex
- W2025935112
- Cited by
- 427
- References
- 157
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 10 · 2023: 18 · 2022: 16 · 2021: 14 · 2020: 23 · 2019: 23 · 2018: 27 · 2017: 39 · 2016: 28 · 2015: 63 · 2014: 51 · 2013: 47 · 2012: 28
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Funders
- Doris Duke Charitable Foundation
- National Institutes of Health (5-R01-)
- National Cancer Institute (5-R01-CA-105118-04, R01CA105118)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Oncology › Advanced Breast Cancer Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mTOR inhibitors, mTOR signaling, mTORC1, mTORC2, PI3K-related kinases, cancer therapy, therapeutic target
- MeSH terms
- Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Phosphoinositide-3 Kinase Inhibitors, Antineoplastic Agents, Clinical Trials as Topic, Female, Humans, Male, Neoplasms, Transcription Factors, Signal Transduction, Phosphatidylinositol 3-Kinases, Sirolimus, Tumor Suppressor Proteins, Protein Kinase Inhibitors, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review